Concerted effects of lipoproteins and angiotensin II on signal transduction processes in vascular smooth muscle cells.

Bochkov, Valery N.; Ткачук, В. А.; Hahn, Alfred W.A.; Bernhardt, J.; Bühler, Fritz R.; Resink, Thérèse J.

doi:10.1161/01.atv.13.9.1261

Cited by 24 publications

(13 citation statements)

References 29 publications

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“…This finding confirms in vitro studies showing that the increase of cytosolic calcium concentration and phosphoinositide content by LDL-C in SMCs was enhanced by Ang II (12). Such an interaction was also shown for the induction of SMC proliferation (13).…”

Section: Discussionsupporting

confidence: 89%

“…Increased vascular levels of Ang II and the expression of its AT1 receptors were found in intimal SMCs of aortas from aging nonhuman primates (10) and in in-stent restenotic lesions of human coronary arteries (11). More importantly, in vitro studies showing synergism between lipoproteins and Ang II in inducing decreased cytosolic calcium concentration (12) and DNA synthesis (13) in vascular SMCs has led to the hypothesis that the effect of mild increases of cholesterol levels on SMC proliferation would be amplified by Ang II. Nonetheless, there are no previously reported in vivo data supporting this concept.…”

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confidence: 99%

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Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Cunha

Martin-McNulty

Vincelette

et al. 2006

Journal of Lipid Research

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Two month old C57BL/6 mice were placed on three different diets: 1) normal diet (NC; 0.025% cholesterol), 2) hypercholesterolemic Western-type diet (HC-W; 0.2% cholesterol), and 3) hypercholesterolemic Paigen-type diet (HC-P; 1.25% cholesterol plus 0.5% cholic acid). At 6 months of age, the animals underwent ligation of the left carotid artery and were randomly assigned to vehicle (PBS, subcutaneous) or angiotensin II (Ang II; 1.4 mg/kg/ day, subcutaneous) treatment for 4 weeks. Low density lipoprotein-cholesterol levels were similarly increased in both HC diets (NC, 4 6 3 mg/dl; HC-W, 123 6 17 mg/dl; HC-P, 160 6 14 mg/dl). However, the levels of high density lipoprotein-cholesterol (HDL-C) were reduced only in animals fed the HC-P diet (NC, 82 6 6 mg/dl; HC-W, 79 6 7 mg/dl; HC-P, 58 6 7 mg/dl). In Ang II-treated mice, carotid artery ligation induced intimal smooth muscle cell proliferation to a similar extent in NC-and HP-W-fed animals. However, a significantly larger intimal area developed in ligated vessels from Ang II-treated mice fed the HC-P diet (3.6-fold higher than in Ang II-treated NC mice). Together, these results show the accelerating effect of mild hypercholesterolemia, reduced HDL-C levels, and Ang II on intimal hyperplasia after carotid artery ligation in mice. Proliferation of smooth muscle cell (SMCs) and migration into the intima is the hallmark of restenosis after vascular interventions (angioplasty, stent or vein graft placement) (1-3) and an important feature of preatherosclerotic lesions (4). It is well established that hypercholesterolemia accelerates atherosclerosis development; however, studies addressing the effect of circulating cholesterol on intimal SMC proliferation have yielded conflicting results. For instance, Theilmeier et al. (5) showed that hypercholesterolemia decreased the population of SMCs in atheromatous lesions in postangioplasty porcine coronary arteries. In contrast, in a recent study, Kahn et al. (6) observed accelerated angioplasty-induced intimal hyperplasia in aortas from hypercholesterolemic rabbits. In both studies, circulating levels of cholesterol were 9-and 18-fold higher than control levels, exceeding the pathophysiologic range of human hypercholesterolemia. Additionally, the concomitant development of spontaneous atheromatous plaque found in these studies adds another important level of interaction between macrophage/foam cell-derived mediators and SMC proliferation (7).In addition to changes in hemodynamic forces (e.g., low shear stress) (8) as predisposing factors for intimal hyperplasia development, locally produced neurohumoral mediators, particularly angiotensin II (Ang II) (9), may be equally important in determining such predisposition. Increased vascular levels of Ang II and the expression of its AT1 receptors were found in intimal SMCs of aortas from aging nonhuman primates (10) and in in-stent restenotic lesions of human coronary arteries (11). More importantly, in vitro studies showing synergism between lipoproteins and Ang II in inducing...

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Cunha

Martin-McNulty

Vincelette

et al. 2006

Journal of Lipid Research

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“…LDL stimulates phosphoinositide turnover and elevates cytosolic calcium levels in vascular smooth muscle cells (40). Minimally modified LDL induces the expression of monocyte adhesion molecules (41), tissue factor (42), MCP-1 (monocyte chemoattractant protein-1) (43), and M-CSF (44) in endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Native and Modified Low Density Lipoproteins Increase the Functional Expression of the Macrophage Class B Scavenger Receptor, CD36

Han¹,

Hajjar²,

Febbraio³

et al. 1997

Journal of Biological Chemistry

237

148

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“…Lipopro teins have been shown to influence secretion and aggrega tion of blood platelets [6][7][8], to regulate vascular tone both via endothelium-dependent mechanisms and direct ac tions on smooth muscle cells [9,10] and to stimulate acti-vation of macrophages [11], Both low-density (LDL) and high-density (HDL) lipoproteins activate phosphatidyl inositol 4,5-bisphosphate-specific phospholipase C [12,13], a central element in the signal transduction systems associated with the regulation of smooth muscle cell con traction and growth. Moreover, synergistic effects be tween lipoproteins and angiotensin II on contraction-cou pled signalling processes in smooth muscle cells [ 14] indi cate that interactions between vasoregulatory hormones and lipoproteins may be functionally relevant to vessel tone/blood pressure regulation.…”

Section: Introductionmentioning

confidence: 99%

Low- and High-Density Lipoproteins as Mitogenic Factors for Vascular Smooth Muscle Cells: Individual, Additive and Synergistic Effects

et al. 1995

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The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and HDL₃ dose-dependently (EC50 values ∼50 µg/ml) stimulated DNA and protein synthesis ([³H]-thymidine and [³H]-leucine incorporation, respectively) in the absence of exogenously added mitogens. The synthetic responses of VSMC to combinations of LDL and HDL₃ were additive, indicating that each lipoprotein mediates discrete effects. LDL or HDL₃ promoted VSMC proliferation under strict mitogen-free conditions, but this growth response was not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL₃) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL₃, VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized, acetylated, carbamylated or malonimylated) also stimulated DNA and protein synthesis. Since the antioxidant β-ydroxylated toluene did not block the effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for the ‘scavenger’ receptor, did not inhibit oxidized LDL-induced DNA synthesis, activation of mitogenic signals by lipoproteins does not depend on lipid peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins may depend upon their direct activation of replication-coupled signal transduction systems.

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Concerted effects of lipoproteins and angiotensin II on signal transduction processes in vascular smooth muscle cells.

Cited by 24 publications

References 29 publications

Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice

Native and Modified Low Density Lipoproteins Increase the Functional Expression of the Macrophage Class B Scavenger Receptor, CD36

Low- and High-Density Lipoproteins as Mitogenic Factors for Vascular Smooth Muscle Cells: Individual, Additive and Synergistic Effects

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